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E-raamat: Industrial Biotechnology: Products and Processes

Series edited by (KAIST,Daejon,Republik Korea), Series edited by (Massachusetts Institute of Technologie, USA), Edited by (University of California, Los Angeles, USA), Series edited by (Chalmers University,Göteborg, S), Edited by (TU Braunschweig, Braunschweig, Germany)
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  • Sari: Advanced Biotechnology
  • Ilmumisaeg: 18-Nov-2016
  • Kirjastus: Blackwell Verlag GmbH
  • Keel: eng
  • ISBN-13: 9783527807840
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  • Formaat: EPUB+DRM
  • Sari: Advanced Biotechnology
  • Ilmumisaeg: 18-Nov-2016
  • Kirjastus: Blackwell Verlag GmbH
  • Keel: eng
  • ISBN-13: 9783527807840
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In industrial biotechnology, a diverse set of microorganisms and biocatalysts is used to produce chemicals, materials and energy in an environmentally friendly and resource efficient way. This book gives an overview about the main product classes and platform chemicals produced by biotechnological processes today, with applications in the food, healthcare and fine chemical industry. For example, chapters deal with the production of drugs and flavors as well as amino acids, bio-based monomers and polymers and biofuels. In addition, basic insights are given to the biotechnological processes yielding such products and how large-scale production can be enabled and improved.

Advanced Biotechnology

Biotechnology is a broad, interdisciplinary field of science, combining biological sciences and relevant engineering disciplines, that is becoming increasingly important as it benefits the environment and society as a whole. Recent years have seen substantial advances in all areas of biotechnology, resulting in the emergence of brand new fields. To reflect this progress, Sang Yup Lee (KAIST, South Korea), Jens Nielsen (Chalmers University, Sweden), and Gregory Stephanopoulos (MIT, USA) have joined forces as the editors of a new Wiley-VCH book series. Advanced Biotechnology will cover all pertinent aspects of the field and each volume will be prepared by eminent scientists who are experts on the topic in question.
List of Contributors xxi
About the Series Editors xxxi
Preface xxxiii
Part I Enabling and Improving Large-Scale Bio-production 1(158)
1 Industrial-Scale Fermentation
3(52)
Hans-Peter Meyer
Wolfgang Minas
Diego Schmidhalter
1.1 Introduction
3(2)
1.2 Industrial-Scale Fermentation Today
5(13)
1.2.1 Organisms Used in Large-Scale Fermentation
5(2)
1.2.2 Contemporary Large-Scale Fermentation
7(7)
1.2.3 Economic Aspects of Industrial Fermentation from a Market Perspective
14(1)
1.2.4 The Drivers and the Future of Industrial Fermentation
15(3)
1.3 Engineering and Design Aspects
18(18)
1.3.1 Process Development - Scale-Up Starts at Laboratory Scale
18(1)
1.3.2 Plant Design Aspects
19(1)
1.3.2.1 General Aspects of Plant Design
19(1)
1.3.2.2 Design Constraints and Guidelines
21(1)
1.3.2.3 Seed Lines
24(1)
1.3.2.4 Vessel Geometry
25(1)
1.3.2.5 Mixing and Mass Transfer
27(1)
1.3.2.6 Temperature Control and Heat Transfer
31(1)
1.3.2.7 Oxygenation
32(4)
1.4 Industrial Design Examples
36(6)
1.4.1 Cephalosporin C Production
36(3)
1.4.2 Monoclonal Antibody Production at the 10 m3 Scale
39(3)
1.4.3 Nonsterile Fermentations
42(1)
1.5 Cost Analysis for the Manufacture of Biotechnological Products
42(5)
1.5.1 Investment
42(1)
1.5.2 Operational Cost, Cost of Manufacturing
43(4)
1.5.3 Return on Invested Capital
47(1)
1.6 Influence of Process- and Facility-Related Aspects on Cost Structure
47(4)
1.6.1 Process-Related Aspects
48(1)
1.6.2 Site-Related Aspects
48(3)
Acknowledgments
51(1)
References
52(3)
2 Scale-Down: Simulating Large-Scale Cultures in the Laboratory
55(26)
Alvaro R. Lara
Laura A. Palomares
Octavio T. Ramirez
2.1 Introduction
55(1)
2.2 Heterogeneities at Large Scale and the Need for Scaling Down
56(2)
2.3 Bioreactor Scale-Down
58(4)
2.4 Tools to Study Cell Responses to Environmental Heterogeneities
62(6)
2.4.1 Scale-Down Simulators
62(1)
2.4.1.1 One-Compartment Scale-Down Systems
63(1)
2.4.1.2 Multicompartment Scale-Down Systems
64(2)
2.4.2 Analytical Techniques
66(1)
2.4.2.1 Metabolic Studies
66(1)
2.4.2.2 Differential Gene Expression and Protein Accumulation
67(1)
2.4.2.3 Physical Measurements
67(1)
2.4.2.4 Mathematical Modeling
68(1)
2.5 Physiological Effects of Environmental Heterogeneities
68(4)
2.5.1 Negative Effects
68(1)
2.5.1.1 Negative Effects on Animal Cells
70(1)
2.5.2 Positive Effects
71(1)
2.5.3 Further Observations
72(1)
2.6 Improvements Based on Scale-Down Studies: Bioreactor Design and Cell Engineering
72(1)
2.7 Perspectives
73(1)
Acknowledgment
74(1)
References
74(7)
3 Bioreactor Modeling
81(48)
Rob Mudde
Henk Noorman
Matthias Reuss
3.1 Large-Scale Industrial Fermentations: Challenges for Bioreactor Modeling
81(2)
3.1.1 Global Status
81(1)
3.1.2 Perspectives
82(1)
3.2 Bioreactors
83(6)
3.2.1 Stirred-Tank Bioreactors
83(3)
3.2.2 Bubble Columns and Air-Lift Reactors
86(1)
3.2.3 Other Reactors
86(1)
3.2.4 Bioreactor Modeling
87(2)
3.3 Compartment and Hybrid Multizonal/Computational Fluid Dynamics Approaches for the Description of Large-Scale Bioreactor Phenomena
89(3)
3.3.1 Compartment Models
89(2)
3.3.2 Hybrid Multizonal/CFD Models
91(1)
3.4 Computational Fluid Dynamics Modeling: Unstructured Continuum Approach (Euler-Euler)
92(22)
3.4.1 Introduction
92(1)
3.4.2 Single Phase
93(1)
3.4.2.1 Turbulence Modeling
95(5)
3.4.3 Two-Phase Flow
100(1)
3.4.3.1 Approaches
100(1)
3.4.3.2 Euler-Euler Model
100(1)
3.4.3.3 Interaction Forces
102(1)
3.4.3.4 Turbulence Modeling
103(1)
3.4.4 CFD of Gassed Stirred Tanks
104(1)
3.4.4.1 Bubble Size
105(1)
3.4.4.2 Glucose Uptake
110(1)
3.4.4.3 Oxygen Uptake - Distribution of Dissolved Oxygen
111(1)
3.4.5 Summary of CFD
112(2)
3.5 Computational Fluid Dynamics Modeling: Structured Segregated Approach (Euler-Lagrange)
114(8)
3.5.1 Introduction
114(1)
3.5.2 Euler - Lagarange Modeling
115(2)
3.5.3 Metabolic Structuring
117(1)
3.5.4 Model Simulations and Detailed Insight into Cell Responses to Dynamic Conditions in Large Bioreactors
118(4)
3.6 Conclusion
122(1)
3.7 Outlook
122(2)
References
124(5)
4 Cell Culture Technology
129(30)
Ralf Partner
Uwe Jandt
An-Ping Zeng
4.1 Introduction
129(1)
4.2 Overview of Applications for Cell Culture Products and Tissue Engineering
129(2)
4.3 Fundamentals
131(9)
4.3.1 Cell Sources
131(1)
4.3.2 Cell Physiology and Kinetics for Process Engineering
132(2)
4.3.3 Population Dynamics, Cell-Cycle Dependence, and Implications on Process Control
134(1)
4.3.3.1 Separation Methods and Analytics
135(1)
4.3.3.2 Population-Resolved Modeling and Data Treatment
136(1)
4.3.3.3 Population-Resolved Online Monitoring and Process Control
138(1)
4.3.4 Medium Design
139(1)
4.4 Bioreactors for Cell Culture
140(6)
4.4.1 Requirements
140(2)
4.4.2 Bioreactors for Suspended Cells
142(2)
4.4.3 Single-Use Bioreactors
144(1)
4.4.4 Fixed-Bed and Fluidized-Bed Reactors
144(1)
4.4.5 Hollow-Fiber and Membrane Reactors
145(1)
4.4.6 Process Strategies and Control
145(1)
4.5 Downstream
146(4)
4.6 Regulatory and Safety Issues
150(2)
4.7 Conclusions and Outlook
152(1)
References
152(7)
Part II Getting Out More: Strategies for Enhanced Bioprocessing 159(78)
5 Production of Fuels and Chemicals from Biomass by Integrated Bioprocesses
161(26)
Tomohisa Hasunuma
Akihiko Kondo
5.1 Introduction
161(2)
5.2 Utilization of Starchy Biomass
163(3)
5.2.1 Pretreatment and Enzymatic Hydrolysis of Starch
163(1)
5.2.2 Consolidated Bioprocessing for Starch Utilization
164(2)
5.3 Utilization of Lignocellulosic Biomass
166(11)
5.3.1 Pretreatment and Enzymatic Hydrolysis of Lignocellulose
166(1)
5.3.2 Consolidated Bioprocessing for Lignocellulose Utilization
167(1)
5.3.2.1 Introduction
167(1)
5.3.2.2 Production of Chemicals with Native Cellulase-Producing Microbes
168(1)
5.3.2.3 Production of Chemicals with Recombinant Cellulose-Utilizing Microbes
169(8)
5.4 Conclusions and Perspectives
177(1)
Acknowledgment
177(1)
References
178(9)
6 Solid-State Fermentation
187(18)
Reeta Rani Singhania
Anil Kumar Patel
Leya Thomas
Ashok Pandey
6.1 Introduction
187(1)
6.2 Fundamentals Aspects of SSF
188(5)
6.2.1 Selection of Microorganisms
188(1)
6.2.2 Specific Growth Rate
189(1)
6.2.2.1 Biomass Measurement
192(1)
6.3 Factors Affecting Solid-State Fermentation
193(3)
6.3.1 Moisture
193(1)
6.3.2 Water Activity
193(1)
6.3.3 Temperature
194(1)
6.3.4 pH
194(1)
6.3.5 Inoculum Type
194(1)
6.3.6 Substrates
194(1)
6.3.6.1 Particle Size
195(1)
6.3.7 Aeration and Agitation
196(1)
6.4 Scale-Up
196(2)
6.4.1 Large-Scale Inoculum Development
196(1)
6.4.2 Medium Sterilization
196(1)
6.4.3 Aeration and Agitation
197(1)
6.4.4 Heat Removal and Moisture Balance
197(1)
6.4.5 pH Control
198(1)
6.5 Product Recovery
198(2)
6.6 Bioreactor Designing
198(1)
6.6.1 Shallow-Tray Fermenter
199(1)
6.6.2 Column/Fixed-Bed Fermenters
199(1)
6.6.3 Rotating-Drum Bioreactors
199(1)
6.7 Kinetics and Modeling
200(1)
6.8 Applications
201(1)
6.9 Challenges in SSF
202(1)
6.10 Summary
203(1)
References
203(2)
7 Cell Immobilization: Fundamentals, Technologies, and Applications
205(32)
Xumeng Ge
Liangcheng Yang
Jianfeng Xu
7.1 Introduction
205(1)
7.2 Fundamentals of Cell Immobilization
206(1)
7.3 Immobilization with Support Materials
207(5)
7.3.1 Surface Attachment
208(1)
7.3.1.1 Adsorption
208(1)
7.3.1.2 Covalent Binding
209(1)
7.3.1.3 Biofilm Formation
209(1)
7.3.2 Entrapment
210(1)
7.3.2.1 Entrapment in Gel Matrixes
210(1)
7.3.2.2 Entrapment in Porous Particles
210(1)
7.3.3 Encapsulation
211(1)
7.3.4 Membrane Retention
212(1)
7.4 Self-Immobilization
212(6)
7.4.1 Microorganisms
213(1)
7.4.1.1 Prokaryotic Cells
213(1)
7.4.1.2 Eukaryotic Cells
214(4)
7.4.2 Plant Cells
218(1)
7.5 Immobilized Cells and their Applications
218(7)
7.5.1 Microorganisms
219(2)
7.5.2 Plant Cells
221(1)
7.5.3 Mammalian and Insect cells
221(4)
7.6 Bioreactors for Cell Immobilization
225(4)
7.6.1 Stirred-Tank Bioreactor
226(1)
7.6.2 Packed-Bed Bioreactor
227(1)
7.6.3 Fluidized-Bed Bioreactor
227(1)
7.6.4 Air-Lift Bioreactor
228(1)
7.6.5 Membrane Bioreactor
228(1)
7.7 Challenges and Recommendations for Future Research
229(1)
7.8 Conclusions
230(1)
References
231(6)
Part III Molecules for Human Use: High-Value Drugs, Flavors, and Nutraceuticals 237(100)
8 Anticancer Drugs
239(32)
Le Zhao
Zengyi Shao
Jacqueline V. Shanks
8.1 Natural Products as Anticancer Drugs
239(1)
8.2 Anticancer Drug Production
239(4)
8.2.1 Production Systems
239(2)
8.2.2 Approaches for Improving Production
241(1)
8.2.3 Gene Discovery
242(1)
8.3 Important Anticancer Natural Products
243(18)
8.3.1 Vinca Alkaloids
243(7)
8.3.2 Taxane Diterpenoids
250(6)
8.3.3 Podophyllotoxin Lignans
256(2)
8.3.4 Camptothecin Quinoline Alkaloids
258(3)
8.4 Prospects
261(2)
8.4.1 Identification of Intermediates in the Biosynthetic Pathways of Anticancer Drugs
261(1)
8.4.2 Discovery of Unknown Genes in Biosynthetic Pathways
262(1)
8.4.3 Production of Anticancer Drugs in Microbial Hosts
262(1)
References
263(8)
9 Biotechnological Production of Flavors
271(38)
Maria Elisabetta Brenna
Fabio Parmeggiani
9.1 History
271(1)
9.2 Survey on Today's Industry
272(1)
9.3 Regulations
273(1)
9.4 Flavor Production
274(1)
9.5 Biotechnological Production of Flavors
275(2)
9.5.1 Traditional Fermentations
275(1)
9.5.2 De novo Synthesis
276(1)
9.5.3 Bioconversions
277(1)
9.6 Vanillin
277(4)
9.6.1 From Eugenol
278(1)
9.6.2 From Isoeugenol
278(2)
9.6.3 From Ferulic Acid
280(1)
9.6.4 From Lignin
281(1)
9.7 2-Phenylethanol
281(2)
9.8 Benzaldehyde
283(2)
9.9 Lactones
285(4)
9.10 Raspberry Ketone
289(2)
9.11 Green Notes
291(2)
9.12 Nootkatone
293(3)
9.13 Future Perspectives
296(1)
References
297(12)
10 Nutraceuticals (Vitamin C, Carotenoids, Resveratrol)
309(28)
Sanjay Guleria
Jingwen Zhou
Mattheos A.G. Koffas
10.1 Introduction
309(1)
10.2 Vitamin C
310(7)
10.2.1 Production of L-AA by Chemical Synthesis
311(1)
10.2.2 Production of L-AA by a Two-Step Fermentation Process
311(1)
10.2.3 Classical Two-Step Fermentation Process
312(1)
10.2.4 New Two-Step Fermentation Process
313(1)
10.2.5 Production of L-AA by a One-Step Fermentation Process
314(1)
10.2.6 Classical Two-Step Fermentation Process-Based Attempts
314(2)
10.2.7 New Two-Step Fermentation Process-Based Attempts
316(1)
10.2.8 Reconstruction of L-AA Biosynthesis Pathway from Higher Organisms in Microorganisms
316(1)
10.3 Carotenoids
317(6)
10.3.1 Biosynthesis of Carotenoids
319(2)
10.3.2 Metabolic Engineering of Carotenoid Biosynthesis in Microbes
321(2)
10.4 Resveratrol
323(6)
10.4.1 Biosynthesis of Resveratrol and Its Derivatives
324(3)
10.4.2 Metabolic Engineering of Resveratrol and its Derivatives
327(2)
10.5 Future Perspectives
329(1)
References
330(7)
Part IV Industrial Amino Acids 337(54)
11 Glutamic Acid Fermentation: Discovery of Glutamic Acid-Producing Microorganisms, Analysis of the Production Mechanism, Metabolic Engineering, and Industrial Production Process
339(22)
Takashi Hirasawa
Hiroshi Shimizu
11.1 Introduction
339(1)
11.2 Discovery of the Glutamic Acid-Producing Bacterium C.glutamicum
340(2)
11.2.1 Glutamic Acid Production Prior to the Discovery of Glutamic Acid-Producing Microorganisms
340(1)
11.2.2 Discovery of C. glutamicum, a Glutamic Acid-Producing Bacterium
340(2)
11.2.3 Characteristics of C. glutamicum
342(1)
11.3 Analysis of the Mechanism of Glutamic Acid Production by C. glutamicum
342(8)
11.3.1 Relationship between Cell-Surface Structure and Glutamic Acid Production in C. glutamicum
343(2)
11.3.2 Metabolic Regulation during Glutamic Acid Overproduction in C. glutamicum
345(1)
11.3.2.1 Biosynthesis of Glutamic Acid in C. glutamicum
345(1)
11.3.2.2 Relationship between Enzyme Activity of the 2-Oxoglutarate Dehydrogenase Complex and Glutamic Acid Production
346(1)
11.3.2.3 OdhI Decreases the Enzymatic Activity of the 2-Oxoglutarate Dehydrogenase Complex
347(1)
11.3.2.4 Anaplerotic Reactions in Glutamic Acid Overproduction
348(1)
11.3.3 Involvement of a Mechanosensitive Channel, NCg11221, in Glutamic Acid Secretion in C. glutamicum
349(1)
11.4 Metabolic Engineering of C. glutamicum for Glutamic Acid Production
350(2)
11.4.1 Metabolic Engineering
350(1)
11.4.2 Metabolic Flux Analysis in Glutamic Acid Production
351(1)
11.4.2.1 Analysis of the Impact of Activities of Enzymes Related to Glutamic Acid Production on the Flux of Glutamic Acid Production
351(1)
11.4.2.2 Use of 13C-MFA to Investigate the Importance of Anaplerotic Reactions to Glutamic Acid Production
351(1)
11.4.3 Metabolic Engineering for Improvement of Glutamic Acid Production
351(1)
11.5 Glutamic Acid Fermentation by Other Microorganisms
352(1)
11.6 Industrial Process of Glutamic Acid Production
353(1)
11.7 Future Perspectives
354(1)
References
355(6)
12 L-Lysine
361(30)
Volker F. Wendisch
12.1 Uses of L-Lysine
361(2)
12.1.1 Feed Use of Amino Acids
361(1)
12.1.2 Economic Importance and Means of Production of L-Lysine
362(1)
12.2 Biosynthesis and Production of L-Lysine
363(11)
12.2.1 L-Lysine Biosynthesis
363(1)
12.2.2 Strain Development for the Production of L-Lysine
363(1)
12.2.2.1 L-Lysine Transport
365(1)
12.2.2.2 De-bottlenecking L-Lysine Biosynthesis
366(1)
12.2.2.3 NADPH Supply for L-Lysine Production
366(1)
12.2.2.4 Reduction of Byproducts of L-Lysine Production
367(1)
12.2.2.5 Precursor Supply for L-Lysine Production
367(1)
12.2.3 Industrial Processes of L-Lysine Production
368(1)
12.2.4 Flexible Feedstock Concept of C. glutamicum: Engineering Carbon Source Utilization
369(1)
12.2.4.1 Molasses, Glucose, Fructose, Sucrose, and Starch
370(1)
12.2.4.2 Lignocellulosics, Cellulose, Xylose, Arabinose, Acetate, Galactose
371(1)
12.2.4.3 Silage Juice and Lactic Acid
373(1)
12.2.4.4 Amino Sugars
373(1)
12.2.4.5 Dicarboxylic Acids
374(1)
12.2.4.6 Glycerol
374(1)
12.3 The Chassis Concept: Biotin Prototrophy and Genome Reduction
374(3)
12.3.1 Engineering Biotin Prototrophic C. glutamicum
375(1)
12.3.2 Genome-Streamlined C. glutamicum Strains
375(2)
12.4 L-Lysine Biosensors for Strain Selection and on-Demand Flux Control
377(3)
12.4.1 Transcriptional Regulators as Diagnostic Metabolite Sensors for Screening
377(2)
12.4.2 Riboswitches as Metabolite Sensors for on-Demand Metabolic Flux Control
379(1)
12.5 Perspective
380(1)
References
380(11)
Part V Bio-Based Monomers and Polymers 391(82)
13 Diamines for Bio-Based Materials
393(18)
Judith Becker
Christoph Wittmann
13.1 Introduction
393(2)
13.2 Diamine Metabolism in Bacteria
395(1)
13.3 Putrescine - 1,4-Diaminobutane
395(4)
13.3.1 Metabolism of Putrescine
396(1)
13.3.2 Biosynthesis and Pathway Regulation
396(2)
13.3.3 Metabolic Engineering for Putrescine Production
398(1)
13.4 Cadaverine - 1,5-Diaminopentane
399(4)
13.4.1 Metabolism of Diaminopentane
399(1)
13.4.2 Biosynthesis and Pathway Regulation
400(1)
13.4.3 Metabolic Engineering for Cadaverine Production
400(3)
13.4.4 Bio-Based Polyamide PA5.10 - A Success Story
403(1)
13.5 Conclusions and Perspectives
403(1)
References
404(7)
14 Microbial Production of 3-Hydroxypropionic Acid
411(42)
Yokimiko David
Young Hoon Oh
Mary Grace BayIon
Kei-Anne Baritugo
Jeong Chan Joo
Cheol Gi Chae
You Jin Kim
Si Jae Park
14.1 Introduction
411(2)
14.2 3-HP Obtained from Native Producers
413(4)
14.2.1 3-HP as an Intermediate of CO2 Fixation
413(2)
14.2.2 Degradation Pathways
415(1)
14.2.2.1 Acrylic Acid
415(1)
14.2.2.2 Pyrimidines (Uracil and Thymine)
415(2)
14.2.3 3-HP as a Nematicide
417(1)
14.3 Synthesis of 3-HP from Glucose
417(4)
14.4 Synthesis of 3-HP from Glycerol
421(16)
14.4.1 CoA-Independent dha Operon
422(3)
14.4.2 CoA-Dependent pdu Operon
425(1)
14.4.3 Redirecting the Flux toward 3-HP Production
426(1)
14.4.4 K. pneumoniae as a Host for Glycerol-Derived 3-HP Production
426(5)
14.4.5 3-HP Production from Glycerol in Recombinant E. coli
431(6)
14.5 Bridging the Gap Between Glucose and Glycerol in 3-HP Production
437(1)
14.6 Other Strains for 3-HP Production from Glycerol
438(2)
14.7 Limitations of 3-HP Synthesis
440(2)
14.8 Conclusions and Future Prospects
442(1)
Acknowledgments
443(1)
References
444(9)
15 Itaconic Acid - An Emerging Building Block
453(20)
Matthias G. Steiger
Nick Wierckx
Lars M. Blank
Diethard Mattanovich
Michael Sauer
15.1 Background, History, and Economy
453(2)
15.2 Biosynthesis of Itaconic Acid
455(4)
15.2.1 Aspergillus terreus
455(1)
15.2.2 Genes and Enzymes Involved in the Biosynthesis of Itaconic Acid in A. terreus
455(4)
15.2.3 Genes and Enzymes Involved in the Biosynthesis of Itaconic Acid in Ustilago maydis
459(1)
15.3 Production Conditions for Itaconic Acid
459(2)
15.4 Physiological Effects and Metabolism of Itaconic acid
461(1)
15.5 Metabolic Engineering for Itaconic Acid Production
462(5)
15.6 Outlook
467(1)
Acknowledgments
468(1)
References
469(4)
Part VI Top-Value Platform Chemicals 473(72)
16 Microbial Production of Isoprene: Opportunities and Challenges
475(30)
Huibin Zou
Hui Liu
Elhussiny Aboulnaga
Huizhou Liu
Tao Cheng
Mo Xian
16.1 Introduction
475(1)
16.2 The Milestones of Isoprene Production
476(1)
16.3 Microbial Production of Isoprene: Out of the Laboratory
477(12)
16.3.1 Advantages of Bioisoprene Against Petroleum-Derived Isoprene
477(1)
16.3.2 Metabolic Pathways and Key Enzyme of Bioisoprene
477(3)
16.3.3 Metabolic Engineering of MVA and MEP Pathways for Microbial Production of Isoprene
480(1)
16.3.4 Substrate for the Microbial Production of Isoprene
481(1)
16.3.5 Evaluation of Isoprene Biosynthetic Process from Different Substrates
482(3)
16.3.6 Chassis Strains for the Microbial Production of Isoprene
485(1)
16.3.7 Recovery Techniques for the Gas-Phase Bioisoprene
486(1)
16.3.8 Scale-up Fermentation and Process Control of Bioisoprene
487(2)
16.4 Main Challenges for Bioisoprene Production
489(2)
16.5 Future Prospects
491(7)
16.5.1 Rational Design of Central Metabolic Pathway to Increase the Yield and Productivity of Isoprene
491(1)
16.5.2 Improving the Yield via Metabolic Pathways (MVA/MEP) Engineering
492(2)
16.5.3 Improving the Intermediate Precursors via Enzyme Engineering
494(1)
16.5.4 Novel Substrates for Bioisoprene
494(1)
16.5.5 Integration of Bio and Chemo Substrates and Process for Isoprene Production
495(1)
16.5.6 Novel Hosts for Isoprene Production
495(1)
16.5.7 Exploring Anaerobic Routes
496(1)
16.5.8 Biosynthesis of Value-Added Isoprene Derivatives
497(1)
Acknowledgments
498(1)
References
498(7)
17 Succinic Acid
505(40)
Jung Ho Ahn
Yu-Sin Jang
Sang Yup Lee
17.1 Introduction
505(1)
17.2 Development of Succinic Acid Producers and Fermentation Strategies
506(27)
17.2.1 Actinobacillus succinogenes
507(3)
17.2.2 Anaerobiospirillum succiniciproducens
510(2)
17.2.3 Corynebacterium glutamicum
512(3)
17.2.4 Escherichia coli
515(11)
17.2.5 Mannheimia succiniciproducens
526(4)
17.2.6 Saccharomyces cerevisiae
530(3)
17.3 Succinic Acid Recovery and Purification
533(3)
17.3.1 Precipitation
533(1)
17.3.2 Electrodialysis
534(1)
17.3.3 Reactive Extraction
535(1)
17.3.4 Adsorption
536(1)
17.4 Summary
536(1)
Acknowledgments
537(1)
References
537(8)
Part VII Biorenewable Fuels 545(52)
18 Ethanol: A Model Biorenewable Fuel
547(26)
Tao Jin
Jieni Lian
Laura R. Jarboe
18.1 Introduction
547(2)
18.2 Metabolic Engineering: Design, Build, Test, Learn
549(14)
18.2.1 Design: Metabolic Pathway Engineering
550(1)
18.2.1.1 Introduction of a Foreign Pathway to Enable Non-native Substrate Utilization
550(1)
18.2.1.2 Introduction of a Foreign Pathway to Enable Homoethanol Production
552(1)
18.2.1.3 Selection of Metabolic Pathways for Modification
554(1)
18.2.1.4 Metabolic Engineering to Enable Mixed-Substrate Utilization
554(1)
18.2.1.5 Selection of Pathway Components for Tuning
555(1)
18.2.2 Design: Membrane Engineering for Improved Tolerance
555(1)
18.2.3 Build: Targeted Genetic Manipulation Techniques
556(1)
18.2.3.1 One-Step Chromosomal Editing of E. coli
556(1)
18.2.3.2 Shuttle Vectors for S. cerevisiae Engineering
556(1)
18.2.3.3 CRISPR/Cas 9
557(1)
18.2.4 Build: Evolutionary Strain Improvement
557(1)
18.2.4.1 Genome-Wide Evolution for Improved Tolerance and Production
557(1)
18.2.4.2 Enzyme Evolution to Enable Nonrecombinant Homoethanol Production
558(1)
18.2.5 Test: Screening of Expression Libraries
559(1)
18.2.5.1 Expression Libraries Containing Sequence Variants of a Preselected Gene
559(1)
18.2.5.2 Expression Libraries that Alter Gene Abundance
560(1)
18.2.5.3 Expression Libraries that Vary Genomic Integration Site
560(1)
18.2.6 Learn: Identifying Strategies and Targets for the Next Design Stage
561(1)
18.2.6.1 Reverse Engineering of Improved Strains
561(1)
18.2.6.2 Learn: Identification of Metabolic Burdens During Production
562(1)
18.3 Biomass Deconstruction
563(1)
18.4 Closing Remarks
564(1)
Acknowledgments
564(1)
References
564(9)
19 Microbial Production of Butanols
573(24)
Sio Si Wong
Luo Mi
James C. Liao
19.1 Introduction
573(1)
19.2 A Historical Perspective of n-Butanol Production
574(1)
19.3 ABE Fermentation
575(5)
19.3.1 The Biochemistry of ABE Fermentation
575(2)
19.3.2 Developing Genetics Tools in Clostridium acetobutylicum
577(1)
19.3.3 Metabolic Engineering of Clostridium acetobutylicum for Butanol Fermentation
578(2)
19.4 n-Butanol Production in Non-native Producers
580(3)
19.4.1 Rationale for Using Non-native Producers
580(1)
19.4.2 Pathways for n-Butanol Biosynthesis
580(2)
19.4.3 Improved n-Butanol Production with Driving Forces
582(1)
19.5 Isobutanol Production
583(6)
19.5.1 The Biochemistry of Isobutanol Production
583(1)
19.5.2 Isobutanol Production from Sugar
584(2)
19.5.3 Isobutanol Production from Cellulose
586(1)
19.5.4 Isobutanol Production from CO2
586(1)
19.5.5 Isobutanol Production from Waste Protein
587(1)
19.5.6 Isobutanol Tolerance of E. coli
588(1)
19.5.7 Other Products from the Keto-Acid Pathway
588(1)
19.6 Summary and Outlook
589(1)
Acknowledgments
589(1)
References
589(8)
Index 597
Christoph Wittmann is Director of the Institute of Systems Biotechnology at Saarland University, Saarbrücken, Germany. Having obtained his academic degrees from Braunschweig Technical University, Germany, he was postdoc at Helsinki University, Finland, held chairs for Biotechnology at Münster University, Germany, and for Biochemical Engineering at Braunschweig Technical University and was invited guest professor at Université Rangueil de Toulouse, France, before taking up his present position. He has authored more than 150 scientific publications, more than 20 books and book chapters, holds more than 20 patents and has received several scientific awards, including the Young Scientist Award of the European Federation of Biotechnology, and is board member of various scientific journals.

James Liao is the Department Chair of Chemical and Biomolecular Engineering at University of California, in Los Angeles (UCLA), USA. Having obtained his PhD degree from University of Wisconsin, Madison, USA, he started his career at Eastman Kodak Company, before moving to Texas A&M, USA, and then UCLA for his academic career. Professor Liao has received numerous scientific awards, including the Presidential Green Chemistry Challenge Award and the ENI award in renewable energy. He is also a member of the US National Academy of Sciences, National Academy of Engineering, and Academia Sinica in Taiwan.

Sang Yup Lee is Distinguished Professor at the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST). He is currently the Director of the Center for Systems and Synthetic Biotechnology, Director of the BioProcess Engineering Research Center, and Director of the Bioinformatics Research Center. He has published more than 500 journal papers, 64 books and book chapters, and more than 580 patents (either registered or applied). He received numerous awards, including the National Order of Merit, the Merck Metabolic Engineering Award, the ACS Marvin Johnson Award, Charles Thom Award, Amgen Biochemical Engineering Award, Elmer Gaden Award, POSCO TJ Park Prize, and HoAm Prize. He currently is Fellow of American Association for the Advancement of Science, the American Academy of Microbiology, American Institute of Chemical Engineers, Society for Industrial Microbiology and Biotechnology, American Institute of Medical and Biological Engineering, the World Academy of Science, the Korean Academy of Science and Technology, and the National Academy of Engineering of Korea. He is also Foreign Member of National Academy of Engineering USA. He is currently honorary professor of the University of Queensland (Australia), honorary professor of the Chinese Academy of Sciences, honorary professor of Wuhan University (China), honorary professor of Hubei University of Technology (China), honorary professor of Beijing University of Chemical Technology (China), and advisory professor of the Shanghai Jiaotong University (China). Lee is the Editor-in-Chief of the Biotechnology Journal and Associate Editor and board member of numerous other journals. Lee is currently serving as a member of Presidential Advisory Committee on Science and Technology (Korea).

Jens Nielsen is Professor and Director to Chalmers University of Technology (Sweden) since 2008. He obtained an MSc degree in Chemical Engineering and a PhD degree (1989) in Biochemical Engineering from the Technical University of Denmark (DTU) and after that established his independent research group and was appointed full Professor there in 1998. He was Fulbright visiting professor at MIT in 1995-1996. At DTU, he founded and directed the Center for Microbial Biotechnology. Jens Nielsen has published more than 350 research papers, co-authored more than 40 books and he is inventor of more than 50 patents. He has founded several companies that have raised more than 20 million in venture capital. He has received numerous Danish and international awards and is member of the Academy of Technical Sciences (Denmark), the National Academy of Engineering (USA), the Royal Danish Academy of Science and Letters, the American Institute for Medical and Biological Engineering and the Royal Swedish Academy of Engineering Sciences.

Professor Gregory Stephanopoulos is the W. H. Dow Professor of Chemical Engineering at the Massachusetts Institute of Technology (MIT, USA) and Director of the MIT Metabolic Engineering Laboratory. He is also Instructor of Bioengineering at Harvard Medical School (since 1997). He received his BS degree from the National Technical University of Athens and his PhD from the University of Minnesota (USA). He has co-authored approximately 400 research papers and 50 patents, along with the first textbook on Metabolic Engineering. He has been recognized by numerous awards from the American Institute of Chemical Engineers (AIChE) (Wilhelm, Walker and Founders awards), American Chemical Society (ACS), Society of industrial Microbiology (SIM), BIO (Washington Carver Award), the John Fritz Medal of the American Association of Engineering Societies, and others. In 2003 he was elected member of the National Academy of Engineering (USA) and in 2014 President of AIChE.